Activation of protein kinase C augments peptide release from rat sensory neurons

J Neurochem. 1996 Jul;67(1):72-80. doi: 10.1046/j.1471-4159.1996.67010072.x.


To determine whether protein kinase C (PKC) mediates release of peptides from sensory neurons, we examined the effects of altering PKC activity on resting and evoked release of substance P (SP) and calcitonin gene-related peptide (CGRP). Exposing rat sensory neurons in culture to 10 or 50 nM phorbol 12,13-dibutyrate (PDBu) significantly increased SP and CGRP release at least 10-fold above resting levels, whereas the inactive 4alpha-PDBu analogue at 100 nM had no effect on release. Furthermore, 100 nM bradykinin increased peptide release approximately fivefold. Down-regulation of PKC significantly attenuated the release of peptides evoked by either PDBu or bradykinin. PDBu at 1 nM or 1-oleoyl-2-acetyl-sn-glycerol at 50 microM did not alter resting release of peptides, but augmented potassium- and capsaicin-stimulated release of both SP and CGRP approximately twofold. This sensitizing action of PKC activators on peptide release was significantly reduced by PKC down-regulation or by pretreating cultures with 10 nM staurosporine. These results establish that activation of PKC is important in the regulation of peptide release from sensory neurons. The PKC-induced enhancement of peptide release may be a mechanism underlying the neuronal sensitization that produces hyperalgesia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bradykinin / pharmacology
  • Calcitonin Gene-Related Peptide / metabolism*
  • Capsaicin / pharmacology
  • Carcinogens / pharmacology
  • Cells, Cultured / enzymology
  • Down-Regulation
  • Enzyme Activation
  • Female
  • Mice
  • Neurons, Afferent / cytology
  • Neurons, Afferent / enzymology*
  • Neuropeptides / metabolism
  • Phorbol 12,13-Dibutyrate / pharmacology
  • Potassium / pharmacology
  • Pregnancy
  • Protein Kinase C / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Sensitivity and Specificity
  • Substance P / metabolism*


  • Carcinogens
  • Neuropeptides
  • Substance P
  • Phorbol 12,13-Dibutyrate
  • Protein Kinase C
  • Calcitonin Gene-Related Peptide
  • Potassium
  • Capsaicin
  • Bradykinin